It is the long term objective of this research project entitled "Polyene Macrolides-Pharmacology and Toxicology" to study the pharmacological properties of the polyene macrolide antibiotics and their biologically-active derivatives with the hope of improved therapeutic application and a full utilization of their inherent clinical potential. The specific objectives include: (1) the preparation by fermentation of a few selected polyene macrolides; (2) the isolation and purification of pure polyene macrolide components; (3) the preparaion of radioactive polyene macrolides by fermentation procedures employing radiocarbon and tritium labeled biochemical precursors; (4) the preparation of biologically active polyene macrolide derivatives by chemical synthesis; (5) the preparation of radioactive polyene macrolide derivatives; (6) the study in laboratory animals including the non-human primate of aspects of the metabolic fate and the overall pharmacological effects of various pure polyene macrolides and their derivatives by oral and parenteral routes of administration; (7) the study of the acute and chronic toxicities of these compounds in small laboratory animals; (8) the study of the in vitro activity of these compounds as well as their in vivo chemotherapeutic efficacy against the fungi, mycoplasma, protozoa, and the lipid-enveloped viruses based on knowledge acquired from pharmacological-toxicological studies; (9) the study of the effect of these compounds as modifiers of the immune system; (10) the study of the effect of these compounds on membrane transport as it applies to chemotherapy; and (11) the availability of polyene macrolides and their derivatives, both unlabeled and radioactive, for NIH authorized pharmacological, biochemical, immunological and chemotherapeutic studies by other investigators.